Hepatic Nodes Research Articles

The significance of hepatic pedicle lymph nodes metastases in surgical management of colorectal liver metastases and of other liver malignancies.

Surgical resection of colorectal liver metastases (CLM) is the only hope for cure, with a 5-year survival rate ranging from 20% to 54%. However, the resectability rate of CLM is reported to be <20%. This limitation is mainly due to insufficient remnant liver and to extrahepatic disease. Among extrahepatic locations, lymph node metastases are often considered indications of a very poor prognosis and a contra-indication to resection. and Our studies showed that the prevalence of hepatic pedicle lymph node metastases ranges from 10% to 20%. When located near the hilum and along the hepatic pedicle (area 1) they should not be considered an absolute contra-indication to resection of CLM, and an extended lymphadenectomy should be performed. However, when they reach the celiac trunk (area 2), there is no survival benefit after resection of CLM. For other cases of liver malignancies, lymph node dissection seems justified only in cases of fibrolamellar hepatocellular carcinoma and in case of hilar cholangiocarcinoma. However, few data are available, and they are controversial. There is a need for more evaluation of lymph node involvement, at least in patients with high risk of such an extension, i.e., patients with more than three metastases, located in segment 4 or 5. There is also a need for prospective trials in order to evaluate the survival benefit of liver resection in such circumstances and the impact of extensive lymphadenectomy.

Metastatic urinary bladder tumor from extragonadal germ cell tumor: A case report

A 37-year old male patient complained of lower back pain. Investigations revealed a retroperitoneal tumor and left-sided cervical lymphadenopathy without abnormal findings in both testicles. The diagnosis of extragonadal germ cell tumor was made based on a lymph node biopsy. Following chemotherapy and retroperitoneal lymphoadenectomy, at outpatient follow-up, beta-HCG elevated again. He complained of gross hematuria, cystoscopy showed a bladder tumor, and abdominal MRI scan showed a right ureteral tumor. Total cystectomy and right nephroureterectomy were performed, which revealed that the bladder and ureteral tumors were metastatic germ cell tumors. Six months later, the patient developed hepatic and mesenteric lymph node metastases that failed to respond to treatment, and died. Germ cell tumors metastasizing to the urinary tract are extremely uncommon, and this is the first report of bladder metastases, other than through direct invasion, from an extratesticular germ cell tumor.

The endoscopic retrograde cholangiopancreatographic manifestations of histopathologically diagnosed hepatocellular carcinoma with obstructive jaundice.

To study the manifestations of endoscopic retrograde cholangiopancreatography (ERCP) in patients of obstructive jaundice associated with HCC, 32 cases of histopathologically diagnosed HCC with obstructive jaundice were successfully examined with routine ERCP. 31 patients were demonstrated by ERCP as having malignant obstructive jaundice. Among them, 19 were hepatic perihilar bile duct stricture, 7 bile ductile tumorous thrombus, 3 perihilar bile duct stricture complicated with thrombus, 2 metastasis to hilar lymph node, and 1 common bile duct stone as proven by sphincterotomy. The malignant perihilar stricture was all of type III and IV by Bismuth standard of Klastin tumor. In patients identified as having bile duct tumor thrombus, by the Ueda classification, none was of type I and II; 1 type III a; 4 III b; 2 type IV. HCC with obstructive jaundice was mainly caused by the malignant infiltration of tumor, and most stricture was of serious nature. When major extra-hepatic bile duct was involved by tumor thrombus, obstructive jaundice might develop. Malignant perihilar stricture and tumor thrombus might coexist in some patients. Jaundice was rarely caused by hepatic hilar lymph node metastasis. Jaundice was not necessarily caused by tumors and sometimes, it might be caused by common bile stones. Care should be exercised in differentiation diagnosis in such patients.

Gallbladder carcinoma with ultrasonographically intact outer hyperechoic layer: A sign of a favorable outcome.

Thirty-one of 40 patients with gallbladder carcinoma whom we treated from December 1983 through June 1999 underwent resection of cancers extending from the mucosa (m) (pTis-pT1a) to the subserosa (ss) (pT2). The patients were classified into five groups according to the layered-structure of the gallbladder wall and the internal echo of tumors visualized in ultrasound images. Group A included pedunculated polyps with round margins, homogeneous hypoechoic internal echoes, and intact outer hyperechoic layers; group B, broad-based lesions with homogeneous hypoechoic internal echoes and intact outer hyperechoic layers; group C, broad-based lesions with intact outer hyperechoic layers and more heterogeneous hypoechoic internal echoes in their centers than those in the marginal lesions; group D, broad-based lesions with irregularity and/or thinning of outer hyperechoic layers; and group E, tumors that could not be evaluated. The ultrasonograms and histopathologic findings of groups A through D were compared, and the surgical techniques used in each group were examined. Outcomes achieved by groups A through C, with their intact outer hyperechoic layers, were compared with those achieved by groups D and E.The six tumors in group A were all well-differentiated adenocarcinomas confined to the mucosa (pTis), and simple cholecystectomy was considered appropriate. The eight tumors in group B comprised three cases of m (pTis-pT1a) cancer, two cases of cancer invading the muscularis propria (mp) (pT1b), and three cases of cancer minutely scattered in the infiltrating subserosal fibrous layer (ss fibrous layer) (pT2). Accordingly, because of the difficulty of determining depth of invasion, resection of the liver bed was considered appropriate in group B. Histopathologic examination of group C showed that the tumors had invaded the ss fibrous layer (pT2) in all six patients. Although the ss fat layer had not been invaded, metastasis to the lymph nodes of the cystic duct (30%) had occurred, suggesting that a favorable outcome could be expected if the patient underwent resection of the liver bed and lymphadenectomy of the cystic duct, pericholedochal, hilar, peripancreatic, periportal, common hepatic, and proper hepatic lymph nodes. Group D comprised two patients with cancers that had invaded the ss fat layer (pT2). All nine tumors in group E were ss (pT2) cancers. The 5-year survival rate was 100 percent in groups A, B, and C; 50 percent in group D, and 45 percent in group E. Five-year survival rates were significantly lower in groups D and E than in groups A, B, and C, in which the outer hyperechoic layer remained intact (p<0.01).Gallbladder carcinomas with intact outer hyperechoic layers were classified into three groups (groups A, B, and C), in which depth of invasion ranged from m (pTis-pT1a) to the ss fibrous layer (pT2). These three groups were associated with favorable outcomes, although different surgical techniques were required for each group. An intact outer hyperechoic layer in the ultrasonogram is a predictor of a favorable outcome in patients with gallbladder carcinoma.

Pathological and Immunohistochemical Study of the Liver and Hepatic Lymph Nodes of Sheep Chronically Reinfected with Fasciola hepatica , with or without Triclabendazole Treatment

Hepatic lesions and changes in the hepatic lymph nodes were examined in groups of sheep infected, and sometimes reinfected, with metacercariae of Fasciola hepatica, with or without treatment with triclabendazole (TCBZ). Hepatic damage was more severe in sheep given small repeated (“trickle”) infections than in those given two larger, spaced doses. Inflammatory infiltrates of eosinophils, CD3 + T cells, CD79α + B cells and IgG + plasma cells, and the presence of granulomata, were particularly marked in trickle-infected groups, suggesting that the host response to certain fluke or egg antigens causes severe hepatic damage. TCBZ administration induced the elimination of flukes and healing of the majority of hepatic lesions but did not prevent severe hepatic damage produced by later infections.

Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: a prospective study.

We investigated whether hepatic pedicle lymph node (HP-LN) involvement is a more significant prognostic factor and whether HP-LN dissection could be efficient in patients with positive HP-LN involvement. From 1988 to 1998, HP-LN dissection was prospectively performed in 160 patients undergoing hepatectomy for colorectal liver metastases. Survival of patients with HP-LN involvement limited to the hepatoduodenal ligament and retropancreatic portion (area 1) was compared with that of patients with HP-LN involvement spreading over the common hepatic artery and celiac axis (area 2). HP-LN involvement was detected in 17 patients. The survival rate was significantly lower in patients with HP-LN involvement. HP-LN involvement was the most significant prognostic factor. Survival was significantly higher in patients with HP-LN involvement limited to area 1 than in those with HP-LN involvement spreading over area 2. HP-LN involvement was the most significant prognostic indicator in patients with colorectal liver metastases. Positive LNs of area 1 should no longer be considered an absolute contraindication to liver resection, but in case of area 2 lymph node involvement, liver resection does not seem justified.

Treatment of metastatic carcinoid tumours with octreotide

It was previously reported that treatment of metastatic carcinoid tumours with octreotide resulted in complete histological regression of such tumours in women.1 Previous cases of octreotide-related regression in carcinoid tumour masses were also reported.2-4 Our recent observation of a patient with hepatic metastases and carcinoid syndrome revealed that even though no discernible regression in tumour mass was found, octreotide treatment led to rapid improvement in hepatic function. A 79-year-old man was admitted to our hospital in November 2000, with a one-month history of facial flushing, headache and pressure in his ears. These attacks lasted 1–2 minutes and occurred several times a day. On examination, a purplish-red facial appearance, conjunctival hyperaemia and an enlarged liver were noted. Cardiac auscultation was within normal limits. Laboratory tests indicated hepatocellular damage and hepatic dysfunction (Table 1). He had no history of heavy alcohol consumption. Serological tests were negative for hepatitis A, B and C viruses. MRI of the abdomen revealed multiple metastases in the liver and multiple lymph nodes up to 2 cm in diameter in the para-aortic area. A liver biopsy was not attempted because of the prolonged partial thromboplastin time. His urinary 5-hydroxyindoleacetic acid level was elevated at 1326 μmol/24 h (normal range: 10.4–31.2). Imaging studies with CT and MR showed no evidence of a primary tumour. Because of the severity of the carcinoid symptoms and signs indicating hepatic dysfunction, we decided to treat this patient with a somatostatin analogue. Octreotide 50 μg three times daily was begun. During a two-week follow-up, the carcinoid symptoms markedly improved. In addition, hepatic function tests noticeably improved. A repeat MRI three weeks after the start of treatment showed no evidence of mass regression. This patient is on follow-up and octreotide treatment is continuing at the same dose for 12 months. The urinary 5-hydroxyindoleacetic acid level decreased to 271 μmol/24 h at month 4 of treatment. Abdominal MRI at 6 and 12 months of treatment showed no evidence of regression in hepatic and intra-abdominal lymph node metastases. He remains well and is still free of symptoms. Serial biochemical evaluation showed no evidence of deterioration in liver function. It is well known that somatostatin analogues have antiproliferative and antimitotic actions. The effect on liver function tests in our patient may not be explained by the decrease in tumour bulk, although we cannot exclude radiographically undetectable tumour regression. Somatostatin and analogues may have direct and indirect effects on hepatocytes and non-parenchymal liver cells.5, 6 Growth factors are able to modify hepatocyte proliferation in vivo, i.e. transforming growth factor β-1 produced by non-parenchymal liver cells is able to inhibit hepatocyte proliferation.7 Inhibitory effects of octreotide on the release of paracrine/growth factors from tumour cells might explain the recovery of liver function in the short term. Whatever the cause, octreotide led to symptomatic and functional recovery of metastatic carcinoid syndrome in our patient.

Significance of Hepatic Pedicle Lymph Node Involvement in Patients With Colorectal Liver Metastases: A Prospective Study

Significance of Hepatic Pedicle Lymph Node Involvement in Patients With Colorectal Liver Metastases: A Prospective Study

Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes.

Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5′-bromo-2′-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-γ–producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-γ leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.

Kupffer cell-mediated recruitment of dendritic cells to the liver crucial for a host defense.

Tissue recruitment of dendritic cells (DCs) is essential for antigen presentation. When latex particulates were injected intravenously into rats, DC precursors were recruited to the liver. Propionibacterium acnes also induced the recruitment of definite mouse DC precursors. These DCs initially showed a selective binding to Kupffer cells. In the Kupffer cell-depleted rats, DCs could neither be recruited to the liver nor adhere to sinusoidal walls. Pretreatment with varied monosaccharides in vitro showed that sugar residues consisting of N-acetylgalactosamine were necessary for this binding. Mouse DC precursors had CC-chemokine receptor 1 and 5, while granulama tissues and rat Kupffer cells expressed the corresponding chemokine, macrophage inflammatory protein-1α. Recruited DC precursors phagocytosed latex or bacteria and some of them soon translocated to hepatic nodes and induced the immune response there. We conclude that after invasion of pathogens, Kupffer cells not only scavenge them but also recruit DCs/DC precursors via chemokine- and N-acetylgalactosamine-mediated interactions. The accelerated DC traffic and the presence of blood-lymph translocation would induce rapid and efficient immune responses and thus contribute to the local defense to antigens within liver tissues as well as systemic defense to blood-borne antigens.

Study of experimentally induced lesions in sheep by grazing Brachiaria decumbens

A histologic and ultrastructural study of the alterations found in the lymph nodes and livers of nine sheep with experimental cholangiohepatopathy by grazing on Brachiaria decumbens has been performed. Sheep were euthanized in three groups, on the 77th, 89th, and 150th days of the experimental feeding. The main gross lesions were whitish spots of multifocal distribution scattered throughout the hepatic parenchyma from all B. decumbens-grazed animals and whitish foci surrounded by reddened halos in the mesenteric and hepatic lymph nodes of sheep necropsied on the 150th. The principal histologic findings included hepatocellular cloudy swelling, marked multifocal cholangitis in the portal triads with bile duct proliferation and infiltration of macrophages and lymphocytes. Crystals were observed within bile ducts and surrounded by macrophages. Ultrastructurally, there were criytaloid structures within the macrophages and hepatocytes, which also presented hyperplasia of smooth endoplasmic reticulum. These findings suggest that hepatocytes were the initial target of the toxic effects, which depending on the degree of severity developed would cause both, subsequent cholangiopathy or occasional photosensitization. Additionally, the developmental stages of the hepatic lesions observed in this study have been presented.

Early hepatic cytokine mRNA expression in experimental rat fasciolosis

We studied the development of the cellular response, particularly with respect to Th1 and Th2 cytokine mRNA levels, in rat liver during the first 14 days of experimental infection with Fasciola hepatica. We analysed the panel of cytokines involved in initiation of the inflammatory and immune response. The levels of various mRNAs, particularly those primarily associated with the acute inflammatory response, and those commonly associated with T-cell proliferation and differentiation, were assessed by reverse transcription-polymerase chain reaction (RT-PCR) in liver samples. We also investigated the immune and inflammatory mediators balance in the liver, draining lymph node and spleen, by RT-competitive PCR quantification of mRNA levels for IL-4, IL-10 and IFN-γ. Our data provide the first evidence that, in the early phase of infection, the inflammatory response in the liver of infected animals is transiently depressed or delayed. A Th0 profile was initially observed in the liver and hepatic lymph node, which developed into a Th2 profile 2 weeks after infection in the liver only. In the spleen, cytokine down-regulation was initiated and maintained during this period, suggesting that the parasite acts differently locally and in the periphery.

Strategy of two-step resection for massive liver cancer

Objective: To investigate the new approach of two-step resection of primary massive liver cancer (PLC). Methods: 10 cases of primary massive liver cancer were treated with two-step resection after marked shrinkage of the tumor by integrating radiotherapy from June 1987 to December 1997. Step one: modified radiotherapy, including radiation of the whole liver by moving split fields and diminution field radiation, plus Traditional Chinese Medicine (TCM) of strengthening the spleen and regulating qi. The total dosage of the radiation was 50–60 Gy. Step two: 3–4 weeks after radiation, resecting the tumor. Results: the diameters of the masses shrinked from 11–15 cm to 6–8 cm after preoperative radiation and TCM. CT showed focus scan one hepatic portal lymph node (2 cm) and a satellite lesions around the tumor (1–3 cm) disappeared after treatment. In one AFP negative case survival cancerous cells was found. The operation did not cause death or serious postoperative complications.

Trafficking of host- and donor-derived dendritic cells in rat cardiac transplantation: allosensitization in the spleen and hepatic nodes.

Kinetics and role of host and donor dendritic cells (DCs) in transplantation immunity are still ill-defined. Using a rat cardiac transplantation model, we studied DC trafficking and sites for allosensitization. Host and donor DCs were defined as host- or donor-type class II major histocompatibility complex antigen single-positive cells by double-immunostaining. Proliferative response of both donor and host cells were also analyzed. Host DCs were recruited to the graft soon after transplantation. These cells represented definitive precursors because of high labeling index by a continuous bromodeoxyuridine infusion, their small round shape, and their putative bone marrow origin. Donor interstitial DCs showed a significant self-replicating capability. Both recruited host DCs in a regraft experiment and donor DCs preferentially performed blood-borne migration to the T-cell area of host spleen. Furthermore, they also migrated to the T-cell area of hepatic lymph nodes after executing the sinusoids-lymph translocation as a novel pathway for these DCs. Selectively at their migration sites, a strong T-cell proliferative response occurred, which preceded that in the graft tissues. Removal of spleen and hepatic lymph nodes significantly prolonged the mean graft survival time. We conclude that allogeneic heart transplantation induces the recruitment of host DC precursors to the graft tissues and the blood-borne migration of both recruited host and donor DCs to the host spleen and hepatic nodes where effector cells are predominantly sensitized.

In vivo roles of donor and host dendritic cells in allogeneic immune response: cluster formation with host proliferating T cells

Possible roles of dendritic cells (DCs) in allogeneic immune responses in host lymphoid tissues were characterized in situ by using rat DC transfer and cardiac transplantation models. When allogeneic DCs were intravenously injected, these cells selectively migrated to the T-cell area of hepatic lymph nodes, with peak accumulation at 18 h after injection. Donor DCs and proliferating host T cells formed clusters (rosettes) in which the T-cell proliferative response started. The donor DCs were CD80(+) CD86(+) and, ultrastructurally, were in intimate contact with lymphoblasts within the rosettes. As a novel finding, some of the migrated donor DCs were quickly phagocytosed by putative host interdigitating DCS: By 48 h, the remaining donor DCs had disintegrated within the rosettes. Host interdigitating DCs also formed rosettes throughout the T-cell area, and their kinetics correlated well with that of the T-cell proliferation. In the cardiac allograft model, a few donor DCs selectively migrated to the host spleen and hepatic nodes. Rosette formation by donor and host DCs, phagocytosis of donor DCs, and the T-cell proliferative response occurred in much the same fashion as they did in the first experiment. We conclude that the donor rosettes at the early stage represent the sites of direct allosensitization and those at the late stage represent donor-DC killing. Host rosettes are the sites of T-cell proliferation. In this structure, phagocytosed donor-DC-derived antigens are presumably indirectly presented.

Comparative Pathogenesis of Infection of Pigs with Hepatitis E Viruses Recovered from a Pig and a Human

Specific-pathogen-free pigs were inoculated with one of two hepatitis E viruses (HEV) (one recovered from a pig and the other from a human) to study the relative pathogenesis of the two viruses in swine. Fifty-four pigs were randomly assigned to three groups. Seventeen pigs in group 1 served as uninoculated controls, 18 pigs in group 2 were intravenously inoculated with the swine HEV recovered from a pig in the United States, and 19 pigs in group 3 were intravenously inoculated with the US-2 strain of human HEV recovered from a hepatitis patient in the United States. Two to four pigs from each group were necropsied at 3, 7, 14, 20, 27, or 55 days postinoculation (DPI). Evidence of clinical disease or elevation of liver enzymes or bilirubin was not found in pigs from any of the three groups. Enlarged hepatic and mesenteric lymph nodes were observed in both HEV-inoculated groups. Multifocal lymphoplasmacytic hepatitis was observed in 9 of 17, 15 of 18, and 16 of 19 pigs in groups 1 to 3, respectively. Focal hepatocellular necrosis was observed in 5 of 17, 10 of 18, and 13 of 19 pigs in groups 1 to 3, respectively. Hepatitis lesions were very mild in group 1 pigs, mild to moderate in group 2 pigs, and moderate to severe in group 3 pigs. Hepatic inflammation and hepatocellular necrosis peaked in severity at 20 DPI and were still moderately severe at 55 DPI in the group inoculated with human HEV. Hepatitis lesions were absent or nearly resolved by 55 DPI in the swine-HEV-inoculated pigs. All HEV-inoculated pigs seroconverted to anti-HEV immunoglobulin G. HEV RNA was detected by reverse transcriptase PCR in feces, liver tissue, and bile of pigs in both HEV-inoculated groups from 3 to 27 DPI. Based on evaluation of microscopic lesions, the US-2 strain of human HEV induced more severe and persistent hepatic lesions in pigs than did swine HEV. Pig livers or cells from the livers of HEV-infected pigs may represent a risk for transmission of HEV from pigs to human xenograft recipients. Since HEV was shed in the feces of infected pigs, exposure to feces from infected pigs represents a risk for transmission of HEV, and pigs should be considered a reservoir for HEV.

Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection.

To assess the status of the regional and paraaortic lymph nodes in hilar cholangiocarcinoma and to clarify the efficacy of systematic extended lymphadenectomy. There have been no studies in which regional and paraaortic lymphadenectomies for hilar cholangiocarcinoma have been routinely performed. Therefore, the metastasis rates to the regional and paraaortic nodes, the mode of lymphatic spread, and the effect of extended lymph node dissection on survival remain unknown. This study involved 110 patients who underwent surgical resection for hilar cholangiocarcinoma with lymph node dissection including both the regional and paraaortic nodes. A total of 2,652 nodes retrieved from the surgical specimens were examined microscopically. Of the 110 patients, 52 (47.3%) had no involved nodes, 39 (35.5%) had regional lymph node metastases, and 19 (17.3%) had regional and paraaortic node metastases. The incidence of positive nodes was significantly higher in the patients with pT3 disease than in those with pT2 disease. The pericholedochal nodes were most commonly involved (42.7%), followed by the periportal nodes (30.9%), the common hepatic nodes (27.3%), and the posterior pancreaticoduodenal nodes (14.5%). The celiac and superior mesenteric nodes were rarely involved. The 3-year and 5-year survival rates were 55.4% and 30.5% for the 52 patients without involved nodes, 31.8% and 14.7% for the 39 patients with regional node metastases, and 12.3% and 12.3% for the 19 patients with paraaortic node metastases, respectively. Of the 19 patients with positive paraaortic nodes, 7 had no macroscopic evidence of paraaortic disease on intraoperative inspection. The survival in this group was significantly better than in the remaining 12 patients. The paraaortic nodes and the regional nodes are frequently involved in advanced hilar cholangiocarcinoma. Whether extended lymph node dissection provides a survival benefit requires further study. However, the fact that long-term survival is possible despite pN2 or pM1 disease encourages the authors to perform an aggressive surgical procedure with extended lymph node dissection in selected patients with hilar cholangiocarcinoma.

Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxesProceedings of a pathology workshop held at the Fraunhofer Institute of Toxicology and Aerosol Research Hannover, Germany, May 7—9, 2001

A Panel of medical and veterinary pathologists reviewed published and unpublished reports dealing with studies of various white mineral oils and waxes in F344 and Sprague-Dawley rats. They also had available and studied histologic slides from both subchronic and chronic studies of certain mineral hydrocarbons (90-day oral study of low melting point wax (LMPW) in female Fischer 344 and Sprague-Dawley rats; 90-day studies of P15H1 and P70H white oil and high melting point wax (HMPW) in male and female F344 rats and 24 month study of P70H white oil in male and female F344 rats. The Panel also reviewed mineral oil-induced alterations in tissues of human patients (liver, hepatic lymph node and spleen). The Panel agreed that certain of the mineral hydrocarbons produced lesions in the mesenteric lymph nodes and liver of the F344 rat and these lesions were best described as microgranulomas/granulomas. The lesions were fundamentally similar in both organs, although varying in severity with dose and type of mineral hydrocarbons. The Panel agreed that hepatic lesions with inflammatory cell infiltration, necrosis, and fibrosis were produced only by feeding of LMPW and the lesions were confined to F344 rats and not found in Sprague-Dawley rats. The most severe granulomatous lesions in the mesenteric lymph nodes were found in high dose LMPW-fed F344 rats. The microgranulomas were similar in subchronic and chronic studies. Also, little difference existed between controls and treated F344 rats in the incidence and severity of the lesions after 2 years of feeding P70H white oil. The Panel agreed that some slight reversibility existed for these lesions, but also agreed that complete resolution was unlikely as regression of the lesions in the rat would likely be slow. The Panel agreed that a minimal severity infiltrate of mononuclear inflammatory cells occurred in the base of the mitral valve in a slightly increased incidence in F344 rats fed LMPW. The Panel concluded that these mitral valve alterations had little if any toxicologic significance as the focal infiltrate was minimal in severity, occurred in controls, occurred in association with murine cardiomyopathy, and were unlike the responses in the liver and mesenteric lymph nodes. The Panel agreed that the lesions observed in the liver and mesenteric lymph nodes of F344 rats exposed to MHCs, especially the LMPW, were different morphologically from changes observed in lymph node, liver, and spleen of humans that were mineral oil-users. These changes in humans are usually found incidentally in tissues taken at biopsy or autopsy. The MHC-induced lesions can be considered incidental and inconsequential in humans.

Assessment of the morphology and significance of the lymph nodal and hepatic lesions produced in rats by the feeding of certain mineral oils and waxes: Proceedings of a pathology workshop held at the Fraunhofer Institute of Toxicology and Aerosol Research Hannover, Germany, May 7—9, 2001

A Panel of medical and veterinary pathologists reviewed published and unpublished reports dealing with studies of various white mineral oils and waxes in F344 and Sprague-Dawley rats. They also had available and studied histologic slides from both subchronic and chronic studies of certain mineral hydrocarbons (90-day oral study of low melting point wax (LMPW) in female Fischer 344 and Sprague-Dawley rats; 90-day studies of P15H* and P70H white oil and high melting point wax (HMPW) in male and female F344 rats and 24 month study of P70H white oil in male and female F344 rats. The Panel also reviewed mineral oil-induced alterations in tissues of human patients (liver, hepatic lymph node and spleen). The Panel agreed that certain of the mineral hydrocarbons produced lesions in the mesenteric lymph nodes and liver of the F344 rat and these lesions were best described as microgranulomas/granulomas. The lesions were fundamentally similar in both organs, although varying in severity with dose and type of mineral hydrocarbons. The Panel agreed that hepatic lesions with inflammatory cell infiltration, necrosis, and fibrosis were produced only by feeding of LMPW and the lesions were confined to F344 rats and not found in Sprague-Dawley rats. The most severe granulomatous lesions in the mesenteric lymph nodes were found in high dose LMPW-fed F344 rats. The microgranulomas were similar in subchronic and chronic studies. Also, little difference existed between controls and treated F344 rats in the incidence and severity of the lesions after 2 years of feeding P70H white oil. The Panel agreed that some slight reversibility existed for these lesions, but also agreed that complete resolution was unlikely as regression of the lesions in the rat would likely be slow. The Panel agreed that a minimal severity infiltrate of mononuclear inflammatory cells occurred in the base of the mitral valve in a slightly increased incidence in F344 rats fed LMPW. The Panel concluded that these mitral valve alterations had little if any toxicologic significance as the focal infiltrate was minimal in severity, occurred in controls, occurred in association with murine cardiomyopathy, and were unlike the responses in the liver and mesenteric lymph nodes. The Panel agreed that the lesions observed in the liver and mesenteric lymph nodes of F344 rats exposed to MHCs, especially the LMPW, were different morphologically from changes observed in lymph node, liver, and spleen of humans that were mineral oil-users. These changes in humans are usually found incidentally in tissues taken at biopsy or autopsy. The MHC-induced lesions can be considered incidental and inconsequential in humans.

A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables.

The objective of this study was to analyze the clinicopathologic variables and the postoperative outcome in patients with mass-forming intrahepatic cholangiocarcinoma (ICC) to identify important factors for predicting postresection prognosis. Although it has been reported that mass-forming ICC has a different etiology and biologic features compared with hepatocellular carcinoma (HCC), patients with ICC have been dealt with clinicopathologically in the same manner as patients with HCC. Sixty patients who underwent hepatectomy for mass-forming ICC with curative intent between 1981 and 1999 were studied. Fourteen preoperative clinical and diagnostic parameters and 12 postoperative surgicopathologic parameters were analyzed. The rate of operative mortality in this patient cohort was 5%, and the overall 1-year, 3-year, and 5-year survival rates were 68%, 35%, and 29%, respectively, with a median survival of 19.6 months. A multivariate analysis revealed that independent negative prognostic factors were 1) hepatic regional lymph node metastasis, 2) multiple tumor presentation, 3) symptomatic tumor, and 4) the presence of vascular invasion. Using these factors, a new staging system was devised: Stage I disease was defined as a solitary tumor without vascular invasion, Stage II disease was defined as a solitary tumor with vascular invasion, Stage IIIA disease was defined as multiple tumors with or without vascular invasion, Stage IIIB disease was defined as any tumor with regional lymph node metastasis, and Stage IV disease was defined as any tumor with distant metastases. The Kaplan-Meier estimated 3-year survival rate and the median survival for each subgroup were 74% for patients with Stage I disease (median survival is the time when the cumulative survival rate of some patients' group declined to 50%; thus, the median survival could not be calculated in patients with Stage I disease because survival was 74% at the latest follow-up), 48% and 26.2 months for patients with Stage II disease, 18% and 16.8 months for patients with Stage IIIA disease, and 7% and 11.2 months for patients with Stage IIIB disease, respectively (P < 0.0001). None of the patients met the criteria for Stage IV disease. The current results support the use of a new staging system for patients with ICC that is simple and predicts well the differences in survival after patients undergo hepatic resection.